5-Oxa-13,14-didehydro-PGF1 compounds

ABSTRACT

This invention comprises certain analogs of the prostaglandins in which the double bond between C-13 and C-14 is replaced by a triple bond. Also provided in this invention, are novel chemical processes and novel chemical intermediates useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.

The present application is a divisional application of Ser. No. 657,739,filed Feb. 13, 1976, now issued as U.S. Pat. No. 4,029,681 on June 14,1977.

The present invention relates to prostaglandin analogs for which theessential material constituting a disclosure therefor is incorporated byreference here from U.S. Pat. No. 4,029,681, issued June 14, 1977.

I claim:
 1. A prostaglandin analog of the formula: ##STR1## wherein D is##STR2## wherein Y₁ is --C.tbd.C--; wherein g is 1, 2, or 3;Wherein m is1 to 5, inclusive; Wherein M₁ is ##STR3## wherein R₅ and R₆ are hydrogenor methyl, with the proviso that one of R₅ and R₆ is methyl only whenthe other is hydrogen; Wherein L₁ is ##STR4## or a mixture of ##STR5##wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same ordifferent, with the proviso that one of R₃ and R₄ is fluoro only whenthe other is hydrogen; and Wherein R₁ is hydrogen, alkyl of one to 12carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive,aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenyl substitutedwith one, two, or three chloro or alkyl of one to 3 carbon atoms,inclusive, or a pharmacologically acceptable cation.
 2. A compoundaccording to claim 1, wherein D is ##STR6##
 3. A compound according toclaim 2, wherein M₁ is ##STR7## and g is
 1. 4. A compound according toclaim 3, wherein R₃, R₄, R₅, and R₆ are all hydrogen.
 5. A compoundaccording to claim 2, wherein M₁ is ##STR8## and g is
 1. 6. A compoundaccording to claim 2, wherein R₃ and R₄ are both hydrogen.
 7. A compoundaccording to claim 6, wherein R₅ is methyl.
 8. A compound according toclaim 6, wherein R₆ is methyl.
 9. 5-Oxa-13,14-didehydro-8β,12α-PGF₁ α,15-methyl ether, a compound according to claim
 8. 10. A compoundaccording to claim 6, wherein R₅ and R₆ are both hydrogen. 11.5-Oxa-13,14-didehydro-8β,12α-PGF₁ α, a compound according to claim 10.12. A compound according to claim 2, wherein at least one of R₃ and R₄is methyl.
 13. A compound according to claim 12, wherein R₃ and R₄ areboth methyl.
 14. A compound according to claim 13, wherein R₅ is methyl.15. 5-Oxa-15,16,16-trimethyl-13,14-didehydro-8β,12α-PGF₁ α, a compoundaccording to claim
 14. 16. A compound according to claim 13, wherein R₆is methyl.
 17. 5-Oxa-16,16-dimethyl-13,14-didehydro-8β,12α-PGF₁ α ,15-methyl ether, a compound according to claim
 16. 18. A compoundaccording to claim 13, wherein R₅ and R₆ are both hydrogen. 19.5-Oxa-16,16-dimethyl-13,14-didehydro-8β,12α-PGF₁ α, a compound accordingto claim
 18. 20. A compound according to claim 2, wherein at least oneof R₃ and R₄ is fluoro.
 21. A compound according to claim 20, wherein R₃and R₄ are both fluoro.
 22. A compound according to claim 21, wherein R₅is methyl. 23.5-Oxa-15-methyl-16,16-difluoro-13,14-didehydro-8β,12.alpha.-PGF₁ α, acompound according to claim
 22. 24. A compound according to claim 22,wherein R₆ is methyl. 25.5-Oxa-16,16-difluoro-13,14-didehydro-8β,12α-PGF₁ α, 15-methyl ether, acompound according to claim
 24. 26. A compound according to claim 22,wherein R₅ and R₆ are both hydrogen. 27.5-Oxa-16,16-difluoro-13,14-didehydro-8β,12α-PGF₁ α, a compound accordingto claim
 26. 28. A compound according to claim 1, wherein D is ##STR9##29. A compound according to claim 28, wherein M₁ is ##STR10## and gis
 1. 30. A compound according to claim 29, wherein R₃, R₄, R₅, and R₆are all hydrogen.
 31. A compound according to claim 28, wherein M₁ is##STR11## and g is
 1. 32. A compound according to claim 31, wherein R₃and R₄ are both hydrogen.
 33. A compound according to claim 32, whereinR₅ is methyl.
 34. A compound according to claim 32, wherein R₆ ismethyl.
 35. 5-Oxa-13,14-didehydro-PGF₁ α, 15-methyl ether, a compoundaccording to claim
 34. 36. A compound according to claim 32, wherein R₅and R₆ are both hydrogen.
 37. 5-Oxa-13,14-didehydro-PGF₁ α, a compoundaccording to claim
 36. 38. A compound according to claim 31, wherein atleast one of R₃ and R₄ is methyl.
 39. A compound according to claim 38,wherein R₃ and R₄ are both methyl.
 40. A compound according to claim 39,wherein R₅ is methyl.
 41. 5-Oxa-15,16,16-trimethyl-13,14-didehydro-PGF₁α, a compound according to claim
 40. 42. A compound according to claim39, wherein R₆ is methyl.
 43. 5-Oxa-16,16-dimethyl-13,14-didehydro-PGF₁α, 15-methyl ether, a compound according to claim
 42. 44. A compoundaccording to claim 39, wherein R₅ and R₆ are both hydrogen. 45.5-Oxa-16,16-dimethyl-13,14-didehydro-PGF₁ α, a compound according toclaim
 44. 46. A compound according to claim 31, wherein at least one ofR₃ and R₄ is fluoro.
 47. A compound according to claim 46, wherein R₃and R₄ are both fluoro.
 48. A compound according to claim 47, wherein R₅is methyl.
 49. 5-Oxa-15-methyl-16,16-difluoro-13,14-didehydro-PGF₁ α, acompound according to claim
 48. 50. A compound according to claim 47,wherein R₆ is methyl.
 51. 5-Oxa-16,16-difluoro-13,14-didehydro-PGF₁ α,15-methyl ether, a compound according to claim
 50. 52. A compoundaccording to claim 47, wherein R₅ and R₆ are both hydrogen. 53.5-Oxa-16,16-difluoro-13,14-didehydro-PGF₁ α, a compound according toclaim 52.